Aim: To further evaluate the antifertility effects of tripchlorolide, a derivative of triptolide produced at the extraction procedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action. Methods: In male rats, tripchlorolide was given by oral garage at a dose of 50 gkg-1d-1 for 5 weeks, fertility was assessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes were also performed. Results: Administration of tripchlorolide at 50 gkg-1d-1 for 3 weeks did not influence the fertility of male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected from cauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and -glucosidase content in the epididymal fluid were decreasd. There were no significant differences in -glucosidase and acid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious morphological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosome curving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In testicular homogenates, tripchlorolide had no influence on the lactate dehydrogenase-C4 (LDH-C4) and hyaluronidase activities. No apparent lesions were observed in the seminiferous and epididymal epithelium. Conclusion: At the dose level employed, tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and testicular and epididymal spermatozoa

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