The present study tested diclofenac's antidepressant properties in albino mice using an IFN-induced depression paradigm. After inflicting stress on albino female mice, the antidepressant effects of a selected medication were evaluated using the locomotor activity, splash test, forced swimming test, tail suspension, sucrose preference, and open field tests. It was noticed how long patients remained still throughout the TST and what percentage of them preferred the sucrose solution. Monitoring brain malondialdehyde (MDA) levels, catalase (CAT) activity, and reduced glutathione (GSH) levels allowed researchers to assess the antioxidant capacity. When compared to the stressed group, animals administered Diclofenac had substantially shorter durations of immobility during the TST. Sucrose solution became more popular after diclofenac treatment, putting it closer to the common antidepressant Amitriptyline. Additionally, diclofenac dramatically lowered brain MDA and catalase activity as well as plasma corticosterone, nitrite, and glutathione levels. However, further investigation is needed to determine if the antidepressant effects of diclofenac are therapeutically useful