Abstract: Background and Objective: Researches have reported that valsartan or melatonin bedtime administration showed a positive therapy to treat non-dipping Blood Pressure (BP), respectively. However, the combined effect of these two drugs in the treatment of non-dipping BP is unknown. Thus, this work aimed to evaluate the combined effects of valsartan and melatonin in the treatment of Spontaneous Hypertension Rats (SHR) with non-dipping BP and to explore its potential mechanism. Materials and Methods: A total of 28 male Wistar-Kyoto rats (WKY) was utilized as a non-disease control. A total of 144 male SHRs were treated with valsartan (10 mg/kg/day) combined with or without melatonin (20 mg/kg/day) after light onset. The 24 hrs BP, ANG II, ET-1, NO, Per1 and Per2 mRNA levels were detected. Nonlinear regression was used to calculate parameters of circadian BP rhythm. Inter-group means were compared using a One-Way Analysis Of Variance (ANOVA). Results: Valsartan administration with or without melatonin can significantly reduce active BP, restored circadian BP rhythm. Moreover, combination therapy reduced plasma levels of ANG II, ET-1 and NO, restored circadian rhythm ANG II in SHR rats and down-regulated the expression of Per1 mRNA in the aorta abdominalis. Conclusion: Melatonin combined with valsartan significantly reduced BP and restored circadian BP rhythm than a single drug. The mechanism may associates with decreased Per genes expression and recover circadian rhythm of plasma ANG II.