Cyclophosphamide (CP), an alkylating agent used in the treatment of several cancers as well as an immunosuppressant in rheumatoid arthritis. It is used against several cancers due to its broad spectrum efficacy, but at the same time possesses unwanted risks for occupational exposure as well as therapy related toxicities to patients. The present study was aimed to investigate the protective effect of astaxanthin (AST) a red carotenoid pigment on CP induced germ cell toxicity in male mice. CP was administered intraperitoneally (i.p.) at the dose of 50, 100 and 200mg/kg body weight to mice (20-25 g) once in a week for a period of five weeks. AST was given at the dose of 25mg/kg per oral (p.o.) for five consecutive days in a week for five weeks. The animals were sacrificed one week after the last injection of CP. The protective effect of AST against CP induced male germ cell toxicity was evaluated using body weight, testes and epididymis weight, sperm count, sperm head morphology, sperm comet assay, histology of testes and TUNEL assay. AST treatment significantly improved the testes weight, sperm count and sperm head morphology as compared to only CP treated animals. The result of comet assay showed that AST treatment significantly restored the sperm DNA damage induced by CP. Further, AST treatment showed protection against CP induced testicular toxicity as evident from testes histology and TUNEL assay. The present results indicate the chemoprotective potential of AST against CP induced germ cell toxicity in mice.