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Objective: To explore the protective effect and its mechanism of the protein and peptide extracts from the muscle of Chinese giant salamanders (SP) on the protection of bisphenol A (BPA)-induced sperm disorder in mice. Methods: Forty male C57BL/6 mice were divided into four groups, Control group, BPA group, BPA+CS group and BPA+SP group. BPA group was injected with 50 mg/kg/d of BPA, which dissolved in corn oil. Control group was injected with corn oil only. The BPA+CS group was given compound substances, which have been proved to be beneficial for spermatogenesis, and were used as controls. The BPA+SP group was given the above mentioned compounds plus SP dissolved in physiological saline. Mice received the compounds plus SP by gavage. The doses were 4 g/kg/d for both groups. The model was established continuously for 28 days, during which the body weight of mice was measured weekly. Testicular volume and testosterone-body ratio were measured after establishment of animal model. Epididymal sperms were collected to measure sperm number and sperm motility by using the computer aided analysis system (CASA). The amount of testosterone in the serum was determined by ELISA. HE staining and TUNEL staining were used to analyze testicular histopathology. Finally, immunofluorescence staining and Western blotting were used to analyze the expression of metastasis associated protein 2 (MTA2), and Oil Red O staining was used to observe the phagocytosis of Sertoli cells in vitro and in vivo. Results: Compared with the control group, the testicular volume (P<0.05), testicular weight (P<0.05), testosterone-body ratio (P<0.05), sperm number (P<0.05), sperm motility (P<0.05), and the amount of testosterone in the serum of mice (P<0.01) in BPA group were significantly decreased. Testicular morphology was damaged and the number of apoptotic spermatogenic cells in BPA group was increased compared with control group(P<0.01). At the same time, the expression of MTA2 and the phagocytosis of Sertoli cells in BPA group were decreased compared with control group (P<0.01). There was no difference between BPA + CS group and BPA group. Surprisingly, the above changes in BPA group were significant difference by using SP(P<0.05). Conclusion: SP has obvious protective effect on BPA-induced sperm disorder in mice, and the mechanism of action may be related to enhanced phagocytosis of Sertoli cells by improving the expression of MTA2. [ABSTRACT FROM AUTHOR]