[Objectives] Hibernation is a very frequent occurrence in animals. During hibernation, the activity and digestive functions of animals are reduced, and the metabolic rate of animals is much lower than the basal metabolic rate, especially in amphibians and reptiles. Research demonstrated that the numbers of glucagon, gastrin, and somatostatin cells in the digestive system of Rana catesbeiana during hibernation were higher than that during the non-hibernation period or not significantly changed. Argyrophilic cells are the general term for the endocrine cells of the digestive tract that regulate the digestion, absorption, and feeding behavior of animals. However, little is known about the changes of argyrophilic cells in the digestive tract of R. catesbeiana pre-hibernation and post-hibernation, so we studied these changes during hibernation. [Methods] As a pre-hibernation experimental group, we acquired 10 R. catesbeiana from the Harbin Hada wholesale aquatic products market in September 2020 and acclimated them for 7 d in the laboratory. As a hibernation phase experimental group, 10 R. catesbeiana were obtained in October 2020 and acclimated to lab settings for 7 d in 6 ℃ incubators until mid-December 2020. April 10, 2021, 7 d under acclimatized laboratory conditions for the post-hibernation experimental group. Each R. catesbeiana was fed a live goldfish weighing around 3.5 g every three days while it was being domesticated. The Grimelius silver staining was applied to the intestinal tract. SPSS 23.0 and Duncan’s multiple range test were applied to make a statistical analysis of the argyrophilic cells in the digestive tract of three periods of R. catesbeiana. An independent sample t-test was applied to compare the distribution density of the argyrophilic cells in the same part of the digestive tract of the three groups, and the data were shown as “mean ± SE”. GraphPad Prism Version 8.0 software was used to plot the data. The argyrophilic cells were photographed using MOTICAM ProS5Lite microimaging system. [Results] The argyrophilic cells in R. catesbeiana digestive tract did not differ morphologically during hibernation, pre-hibernation and post-hibernation, being cone-shaped, fusiformis and ellipse. Cone-shaped and fusiformis argyrophilic cells with exocrine activity in various parts of the R. catesbeiana digestive tract had considerably larger densities in the digestive tract during the three periods than elliptical cells with endocrine function (P < 0.01). In all three phases, the distribution density of argyrophilic cells peaked in the jejunum, while the troughs varied. The distribution densities of argyrophilic cells are lowest in the esophagus during the pre-hibernation and post-hibernation periods, and in the cardia during the hibernation period. Except for the pre-hibernation and hibernation periods, there were differences in the distribution density at the pylorus (P > 0.05), and the distribution densities of the esophagus, stomach, duodenum, jejunum, ileum, and rectum during hibernation were significantly higher than those of the pre-hibernation and post-hibernation periods (P < 0.05). In the pre-hibernation and post-hibernation periods, the argyrophilic cells displayed an inverted “U”-shaped distribution pattern, and in the hibernation phase, a “~”-shaped distribution pattern (Fig. 2). [Conclusion] Overall, the variations in the distribution density of argyrophilic cells in R. catesbeiana during the three time periods were correlated with the physiological states and functions of the major digestive tract components. The distribution density of argyrophilic cells increased dramatically during hibernation compared to pre-hibernation and post-hibernation, which was linked to improved immunological response and an increase in the small intestine’s sensitivity to neurotransmitters. In short, the morphological characteristics of the argyrophilic cells did not change significantly in pre-hibernation and post-hibernation, whilst the number of argyrophilic cells changed to accommodate the regular performance of their digestive activities and endocrine functions.