【Abstract】 Objective To investigate the protective effect of Lubian Renshen Paste on fertility in a busulfan-induced mouse model of oligoasthenozoospermia. Methods A mouse model of oligoasthenozoospermia was established in Kunming mice by intraperitoneal injection of busulfan at 35 mg/kg. The mice were divided into normal control, model control, and low-, medium-, and high-dose Lubian Renshen Paste groups. After model establishment, mice in the low-, medium-, and high-dose groups were administered Lubian Renshen Paste by gavage at 1, 2, and 4 g/(kg·d), respectively, while the normal and model control groups received an equal volume of vehicle for 8 weeks. The effects of Lubian Renshen Paste on mouse reproductive organs and fertility were observed. Results The oligoasthenozoospermia model was successfully established. Compared with the model control group, Lubian Renshen Paste increased the testicular and seminal vesicle indices in model mice (P<0.05). Medium- and high-dose Lubian Renshen Paste increased sperm motility and the proportion of progressively motile sperm (P<0.05). In addition, sperm count was higher in the medium- and high-dose groups than in the model control group (P<0.05). Serum testosterone concentration tended to increase after Lubian Renshen Paste intervention. The mating experiment showed that gestation time was shortened in the medium- and high-dose groups (P<0.05), whereas litter size did not differ significantly among groups (P>0.05). Conclusion Lubian Renshen Paste increased the testicular and seminal vesicle indices and improved sperm quality and mating performance in busulfan-induced oligoasthenozoospermia model mice, suggesting a protective effect on impaired male fertility.