This research was undertaken to determine the effect of cyclophosphamide(CP) on the Leydig cells and macrophages in the interstitial tissue of the mice(ICR strain). To evaluate how this drug could affect the these cells, during administration(200mg/kg) 1 time to 3 times at intervals of 48hrs. In the Leydig cells of the control and 1 time treated group, a number of microperoxisomes were observed interspersed among the network of smooth endoplasmic reticulum(SER) in cellular regions where the SER predominantes. Microperoxisomes were also founded in close proximity to the cell membrane. The interstitial tissue were exhibited degenerating Leydig cells but macrophages wer containd greatly increased numbers of cytoplasmic inclusion body and secondary lysosomes. In the 1 time treated group. A very small number of Leydig cells were observed, from 2 to 3 time group, but macrophages were more increased than 1 time group in number. CP thus offers a valuable opportunity to study further the interaction between Leydig cells and macrophages in the interstitial tissue. These alteration could be direct mediated by toxic effect of the drug on the interstitial tissue.