Objective: To study the toxicity effect of carbon tetrachloride (CCl4) combining with diethylnitrosamine（DEN）on testis in mice. Methods: Kunming mouse were randomly divided into two groups. The experimental group was injected by 15% CCl4 / peanut oil solution intraperitoneally two times a week for eight weeks, and drinking 0.07‰ DEN water solution freely during the treatment. The control group was injected peanut oil and drinking purified water. Both experimental group and control group, four mouse were killed at the 3, 6, 8 weeks respectively. The testicle tissue of mouse was fixed, embedded and cut conventionally, then was stained by HE stain. The changes of testicular structure and the number and shape of sperms were observed. Values were presented as Mean±SD of three independent samples. The results were analysed by two-sample equal variance Student’s t-test (one-tailed), Statistical significance was set at P＜0.05. Results: The average weight significantly increased in control group compared with the experimental group (Tab.1). Testicle organ coefficient and survive rates of the sperms were significantly decreased in experimental group compared with the control group (Tab. 2, 3). The mice of control group have normal seminiferous tubule and a large number of sperm. The testis of mice in the experimental group killed in 3 weeks is similar to the control group, with completed seminiferous tubule and a small amount of the spermatogenic cells. After 6 weeks, the testis in experimental group mice changed, with disordering spermatogenic cells，decreasing and abnormal sperm. After 8 weeks, the testis of experimental group mice had a dramatic change, about all the spermatogenic cells and sperms arranged disorderly, the number of sperm decreased and deformity of sperm increased (Fig. 1). Conclusion：CCl4 combining with DEN can damage testis structure of mice and decrease the number of sperm and induce distortion of sperm.