Objective: To study the gene expression profile of Jinkui Shenqi Wan on the recovery of spermatogenesis in azoospermia mice. Method: Liquid busulfan 2% was injected (ip 40 mg·kg-1) in 12-week-old NIH male mice to prepare azoospermic model. Jinkui Shenqi Wan were administrated to azoospermia mice by gastric irrigation for 78 days (two spermatogenesis cycles) after 42 days of modeling. The testis total mRNAs of Jinkui Shenqi group and normal group were used to study gene expression profile by microarray. Result: The important fertility-related indicators such as body weight

reproductive organs and tissue mass index

sperm quality (motility

activity

concentration) and so on were improved significantly in azoospermia mice treated with Jinkui Shenqi Wan for 78 days. Jinkui Shenqi Wan played significant roles in recovering the spermatogenesis of testis in azoospermia mice. Compared with the normal group

microarray results showed that there were 804 genes (2.53%

517 upregulation

287 downregulation) with more than two times differential expression and 134 genes (0.42%

127 upregulation

7 downregulation) with four times differential expression

respectively. This suggested that the main role of Jinkui Shenqi Wan on recovery of spermatogenesis was positive and upregulation

negative and downregulation played secondery roles. Pathway analysis showed these genes expressed in: cell cycle

cytokine-cytokine receptor

Ecm receptors

Jak-Stat signaling pathway

Mapk signaling pathway

Notch signaling pathway

Toll-like receptor signaling pathway and Wnt signaling pathway. Conclusion: Testis spermatogesis of azoospermia mice can be recovered after administration of Jinkui Shenqi Wan by positive controlling genes related to cell proliferation through different pathways.