OBJECTIVES: Diclofenac (Diclo) is a therapeutic agent used in the treatment of pain and inflammatory diseases, but it is also toxic to the human body. Morin is a flavonoid found naturally in plants and has many biological and pharmacological activities, including anti-inflammatory, anti-oxidant, and anticancer activities. This study aimed to investigate the efficacy of Morin in Diclo-induced testicular toxicity. MATERIALS AND METHODS: Morin (50 mg/kg and 100 mg/kg) was administered orally for five days, while Diclo was administered intraperitoneally at 50 mg/kg on days 4 and 5. Biochemical, molecular, and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and endoplasmic reticulum (ER) stress damage indicators in testicular tissue. RESULTS: Morin treatment attenuated Diclo-induced oxidative stress damage by increasing anti-oxidant levels (SOD, CAT, GPx, GSH, Nrf-2, HO-1, and NQO1) and decreasing MDA levels, an indicator of lipid peroxidation. Morin reduced levels of the inflammatory mediators NF-κB protein. Increases in apoptotic Bax and Caspase-3 by Diclo were reduced by Morin, while decreased antiapoptotic Bcl-2 level was increased. Morin reduced Diclo-induced ER stress injury by decreasing ATF-6, PERK, IRE1, GRP-78, and CHOP levels. Also, Diclo decreased COX-2 levels. CONCLUSION: Overall, Morin may be an effective treatment of choice for testicular tissue damage associated with Diclo toxicity and may reduce the level of damage.