Momordica charantia or bitter melon is a tropical vine of the family Cucurbitaceous widely grown in India. Its fruits have potent anti-oxidant properties due to the presence of tannins, vitamin C and flavonoids. There is much evidence it protects cognitive function and cholesterol level. In addition, there are reports of the effect of a high-fat diet (HFD)on memory. In this study, the effect of bitter melon on spatial memory in rats, following an HFD, in a water maze was examined. In this study, 28 male Wistar rats aged 10 weeks and weighing between 180 and 250 grams were divided into four groups (N=7). Control, High-fat, High-fat + bitter melon, and bitter melon. The control group was fed a standard rat diet, whereas the high-fat groups were fed the same standard diet containing 5% cholesterol for eight weeks, and the treated group received, in addition, 1 g/kg bitter melon fruit powder in their diet, Learning and spatial memory were evaluated by using a Morris Water Maze (MWM) for a six-day period, including five days of training, the last day was the test day (probe day). The high-fat group was fed a high-fat diet for two months, this resulted in reduced learning ability;, this group took longer and travelled a longer distance compared to the control group. However, the administration of bitter melon improved memory function only in the high-fat group. The administration of bitter melon improves spatial-memory performance in rats receiving an HFD. © 2019 Sepehri et al.