Objective: Evidence in mice indicates that limiting food access to the active phase, termed time-restricted feeding (TRF), can prevent diet-induced obesity without the necessity of reducing food intake (FI). We compared TRF with pharmacological treatment using Melanotan 2 (MTII), an appetite suppressor that decreases FI and body weight (BW). We hypothesized that TRF would reduce mean arterial blood pressure (MAP) and be as efficacious as MTII in reducing obesity, and moreover, that morning MTII treatment would be more efficacious than evening MTII treatment. Design and method: High-fat fed rats (6/group) treated with vehicle; MTII at beginning of light phase (AM) and vehicle beginning of dark phase (PM); or vehicle at AM and MTII at PM. The TRF approach utilized rats that had access to high-fat diet 24 hours/day (Control) or 12 hours/day only during dark phase (TRF). Body weight, FI, and body composition were assessed in light/dark for 22 days and MAP (by tail cuff) at day 0 and 21. Results: Feeding patterns were profoundly different between MTII AM and MTII PM groups, and cumulative FI was significantly lower in both MTII groups compared with Control. However, despite differences in feeding patterns, there were no differences in FI or BW between AM and PM MTII. With TRF approach, daily FI, cumulative FI, BW, fat mass, and lean mass were unaffected by TRF. In contrast, change from baseline in MAP at week 3 was significantly (p < 0.05) lower for TRF and MTII (am and pm) compared with high-fat control. However, MTII was not different than TRF. No change in heart rate was observed. Conclusions: In conclusion, the profound differences in feeding patterns between MTII AM and PM did not influence MTII-induced body weight loss. In contrast to mice, TRF does not protect against diet-induced obesity in rats, but does reduces blood pressure, suggesting a role for TRF in lowering obesity-related MAP without the need to reduce FI or BW.