This study examined the effects of dexamethasone on active avoidance learning and brain^H-QNB binding in rats by varying drug treatment and sex. Male and female Sprague Dawley rats (4 months) received either 1 mg dexamethasone in sesame oil or only the vehicle at 08:00 and were subjected to learning trials at 10:00. Following 5 days of testing, the rats were decapitated, brains removed and dissected on ice and than receptor binding study was performed. Blood corticosterone levels were assayed. Dexamethasone treatment improved learning performance in both males and females, however caused an increase in H-QNB binding only in males and only in the cerebellum, hipocampus, frontal and parietal cortices (p<0.05). Furthermore, there was a correlation between muscarinic receptor binding and learning performance in the hippocampus, occipital and frontal cortices. The results show that dexamethasone effects active avoidance learning in rats through the muscarinic cholinergic system and more prominently in males.