Abstract: Cryptosporidium is a common cause of severe diarrhea in immunocompromised people and young children. Cryptosporidium infection was found to be associated with elevation of many cytokines as tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β). These cytokines are key stimulators of prostaglandin synthesis. Prostaglandins may contribute to diarrhea by altering chloride secretion. COX-2 is an inducible enzyme and the expression of the COX-2 gene has been shown to increase in certain inflammatory states. It is known that COX-2 is essential for the synthesis of prostaglandins. There are no studies that define the role of COX-2 in intestinal cryptosporidiosis. The present study was aimed to assess the expression pattern of COX-2 immunohistochemically in the intestine of experimentally infected rats. Also, it was aimed to assess the effectiveness of celecoxib, nitazoxanide, nitazoxanide combined with celecoxib and nitazoxanide combined with azithromycin as anticryptosporidial drugs. It was found that infection with Cryptosporidium caused severe pathological changes in ileal tissue. Also, there was a strong correlation between Cryptosporidium and COX-2 expression in the same tissue. So, it can be said that the inflammatory effect of Cryptosporidium in intestine is mediated through induction of COX-2 but practically "celecoxib" which is an anti COX-2 drug did not represent a significant advance in the treatment of rats infected with Cryptosporidium. On the other hand, treatment of infection by nitazoxanide combined with azithromycin represents a significant advance in the treatment of this infection.