Dexamethasone is a common medicine that is capable of causing malformation in the male reproduct- ive system. The aim of this study was to investigate the effect of melatonin on testis histological changes and Spermatogenesis indexes in adult mice following treatment with dexamethasone. Adult male NMRI mice were divided randomly into four groups: control, dexamethasone (i.p injections, 7mg/kg/day), dexamethasoneþmelatonin and melatonin (i.p injections, 20mg/kg/day). After 7days of treatment, the right testes were studied stereologically and the left testes were used to measure the daily sperm production (DSP). The serum levels of malondialdehyde (MDA), testosterone and total anti- oxidant capacity (TAC) were also measured. The left caudal epididymis was used to analyze sperm parameters. Data were analyzed using one way ANOVA and means were considered significantly differ- ent at p<0.05. A significant decrease in the testis volume, seminiferous tubules volume, the number of spermatocytes, round and long spermatids, Spermatogenesis indexes, sperm parameters such as motility, count, viability, tail length and DSP, serum testosterone level, TAC and the body weight was found in the dexamethasone group compared to the control. Meanwhile a significant swelling of the interstitial tissue and a significant increase in the MDA level was found in the dexamethasone group compared to the control. The above parameters reached the control level in the dexamethaso- neþmelatonin group. Melatonin can compensate for the adverse effects of dexamethasone on sperm parameters and the histology of the seminiferous tubules in mice.