With the increasing incidence of premature ovarian failure (POF) seriously threaten the women's health. Whether cryptotanshinone decreased the granulosa cell apoptosis to improve the POF would be explored. POF mice were conducted with intraperitoneal injection of cyclophosphamide and then treated with cryptotanshinone. The body weight and ovarian weight were recorded. The estrus was detected by vaginal smears. The pathological changes of ovarian were observed with hematoxylin and eosin staining. ELISA assay analyzed the levels of LH, FSH, AMH, E2 and AzpAB in mice serum. The expression of Bcl-2, Bax, KI67 and PCNA in ovarian tissues was detected by Western blot analysis and KI67 expression was also determined by immunohistochemistry. The body weight and ovarian weight were decreased and the pathological results of ovarian were worsen in POF mice. The estrus was decreased in POF mice. The levels of LH, FSH and AzpAB were increased and the levels of AMH and E2 were decreased in POF mice serum. The expression of Bcl-2, KI67 and PCNA was decreased and Bax expression was increased in ovarian tissues of POF mice. Those changes affected by cyclophosphamide could be reversed by cryptotanshinone. Cryptotanshinone could decrease the granulosa cell apoptosis to restore ovarian function.