OBJECTIVE: To investigate the effect and action mechanism of Yu Si Granules (YSG) in the treatment methyl methanesulphonate (MMS)-induced oligoasthenozoospermia (OAZ) in mice. METHODS: Thirty adult male mice were randomly divided into three groups of equal number, normal control, OAZ model control and YSG intervention. The OAZ model was established by oral administration of MMS and the model mice in the YSG intervention group were treated intragastrically with YSG suspension at 0.144 g/100 g of the body weight per day for 48 successive days. Then, all the mice were sacrificed and their epididymides harvested for detection of the sperm count and motility, observation of the morphology of the seminiferous tubules by HE staining, determination of the expressions of the germ cell-, sperm cell-, spermatocyte-, Sertoli cell- and blood-testis barrier-related genes by RT-PCR, and measurement of the levels of oxidative stress in the blood. RESULTS: Compared with the normal control, the OAZ model mice showed significantly decreased sperm count (ï¼»49.2 ± 0.7ï¼½ vs ï¼»23.6 ± 0.4ï¼½ ×107/ml/g, P < 0.05) and sperm motility (ï¼»76.3 ± 0.7ï¼½% vs ï¼»5.0 ± 5.8ï¼½%, P < 0.05), which were both remarkably increased after YSG intervention (ï¼»38.4 ± 0.5ï¼½ ×107/ml/g and ï¼»71.5 ± 0.5ï¼½%) (P < 0.05). The OAZ model mice also exhibited degenerated and atrophic seminiferous tubules, thinner seminiferous epithelia, disorderly arranged cells at different levels, reduced number of sperm in the lumen and unclear layers of germ cells in the epididymis, while those after YSG intervention manifested regularly organized seminiferous tubules with orderly arrangement and clear layers. The expressions of the Vasa, Dazl and Snd1 genes were significantly decreased (P < 0.05), but not those of Gfra, Plzf, Stra8, Spo11, Sycp3, Sox9 and Vim (P > 0.05) in the OAZ model and YSG intervention groups as compared with those in the normal control group. The superoxide dismutase (SOD) activity in the serum was markedly reduced in the OAZ model mice as compared with that in the normal controls (P < 0.05) and increased again after YSP intervention (P < 0.05), but the opposite was the case with the expression of the superoxide anion. CONCLUSIONS: YSG can significantly reduce MMS-induced OAZ in mice, which may be associated with oxidative stress.