The current study was conducted to assess the effect of HFD (40%) on estrous cycle regularity and body weight in female rats. Fourteen female Wistar albino rats were randomly divided into two groups. The control group (I) received the standard chow diet, and the HFD group (II) received the HFD (55% basal diet, 3% sesame oil, 25% beef tallow, 5% milk powder, 5% roasted peanuts, 5% egg, and 2% NaCl) daily for 10 successive weeks. Bodyweight was recorded every week from the beginning of the study to the end, where, at the 8^th week after dietary exposure, the assessment of the estrous cycle was performed daily for ten successive days using visual assessment and vaginal cytology procedures. The HFD group revealed a statistically higher proportion of rats with an irregular estrous cycle (p = 0.031) and a significantly increased diestrus index vs. the control group (p = 0.025). The HFD group revealed a nonsignificant decrease in the cycle frequency, a significant decrease in the total days of the proestrus stage (p ≤ 0.001), and a nonsignificant shortening in the estrus and metestrus stages vs. control. In contrast, the HFD group revealed a significantly longer diestrus stage than the control group (p = 0.025). Weight gain and body weight were significantly increased throughout the experiment in the HFD group when compared with the control group (p < 0.001). In conclusion, HFD results in increased body weight and increased estrous cycle irregularities, which may impair the female reproductive function.