Background:  Chewing Khat (Catha edulis) is widespread in many parts of the world for its stimulating and euphoric effect, although Numerous studies have recently demonstrated the harmful effects of chewing khat.
Aim: examine the impact of saffron in minimizing khat-induced prostate toxicity in male rats.
Materials and methods: Four equal groups of 40 male albino rats were used. Control, Saffron: Saffron extract was given to rats orally at a dose of 100 mg/kg body weight. Khat: Khat extract was orally administered to rats at a dose of 200 mg/kg body weight. And finally, Khat + Saffron: Rats were given the same previous doses of khat and saffron. Result: Rats treated with Khat showed marked changes in the prostate which included degeneration of the glandular lining epithelium with an exfoliation within the lumen, marked edema with dilation in blood vessels, hemorrhage in the interstitial tissue, abnormal flattened epithelial layers of the prostatic acini and Substantial hyperplasia were founded in the prostatic acini's lumens. The histochemical analysis clarified that there was a significant decrease in proteinic and polysaccharide contents. Also, a decrease in the vimentin, E-cadherin proteins, and BCL2 expression while increasing BAX expression. Superoxide dismutase and catalase activity showed a marked decrease while malondialdehyde levels were. elevated. However, rats given both saffron and khat showed less harm than the khat group in prostatic histology. In Conclusion, saffron demonstrated its strong antioxidant feature besides its effectiveness in mitigating and ameliorating the histological changes induced by khat in the prostate of male rats.