The role of cyclooxygenases (COX) in the male reproductive organ remains unclear. However, there are some reports suggesting that COX-2 might have an effect on the spermatogenesis or steroidogenesis. In this study, we examined whether COX-2 was induced in impaired testes, and also investigated the possible role of COX in the testes using experimental cryptorchidism model mice. Five-week-old male mice underwent an operation to induce unilateral cryptorchidism via an abdominal incision and suturing of the left testes to the lateral abdominal wall, and they were then divided into three groups: (1) experimental cryptorchidism plus SC560 (selective COX-1 inhibitor) administration; (2) experimental cryptorchidism plus NS398 (selective COX-2 inhibitor) administration; (3) and experimental cryptorchidism alone. The expression levels of COX-1 and COX-2 were determined by immunohistological staining and the quantitative reverse transcriptional polymerase chain reaction (RT-PCR). The influence of COX inhibitors on the testes was assessed by measuring the concentration of serum testosterone and evaluating the seminiferous tubules according to the Johnsen score (JS). TdT-mediated dUTP-biotin nick end-labeling (TUNEL) staining was also performed to detect apoptosis in the testes. Immunohistological staining and RT-PCR revealed that the expression of COX-2 was increased in the experimental cryptorchid testes (Groups 1-3). The concentration of serum testosterone was significantly lower in Group 2 at five weeks after surgery than in the other groups. The Johnsen score of the cryptorchid testes in Group 2 was significantly lower than those in other groups at five weeks after surgery. TUNEL staining revealed that the number of apoptotic cells was significantly increased in Group 2 compared with the other groups. However, the COX-1 inhibitor did not appear to affect spermatogenesis in the experimental cryptorchid testes. These results suggest that the COX-2 inhibitor provoked testicular damage in experimental cryptorchidism by inducing germ cell apoptosis. The expression of COX-2 might be induced to protect germ cells from heat stress caused by experimental cryptorchidism.