Objective To explore the effect of unpredictable chronic mild stress (UCMS) on rats' blood pressure and depressive behaviors and the therapeutic method. Methods A total of 15 Wistar-Kyoto (WKY) rats, and 15 spontaneously hypertensive rats (SHR), were respectively divided into three groups, including the control group, UCMS group, and UCMS+treatment group (n=5). The control group was treated with saline for four weeks; the UCMS group was treated with seven kinds of stress for 21 days; the UCMS+treatment group was treated with both UCMS for 21 days and traditional Chinese medicine (Guanxindanshen dropping pills) for four weeks. Tail-cuff was performed to detect heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). Sucrose preference test and open field test were applied to detect depressive behaviors. SPSS 24.0 was used for statistic analysis, such as student's t-test for two group comparisons and Oneway ANOVA for multiple groups comparisons. Results Compared with the control group, WKY rats with UCMS had a significantly lower level of DBP [(98.2±13.2) mmHg vs. (56.4±13.8) mmHg, 1 mmHg=0.133kPa, P<0.05], MAP [(103.8±13.2) mmHg vs. (69.2±10.1) mmHg, P<0.05]; While no significant difference of hemodynamic indexes in SHR. Compared with the control group of WKY rats, sucrose preference decreased significantly after UCMS [(79.0±2.3)% vs. (67.5±6.8)%, P<0.05]; cross-grid times decreased significantly [(50.2±8.5) times vs. (33.4±6.2) times, P<0.05], standup times decreased [(8.0±1.6) times vs. (4.2±0.8) times, P<0.05]. Compared with the control group, after UCMS, SHR had fewer sucrose water [(11.0±1.9) g vs. (8.0±1.6) g, P<0.05], higher pure water [(3.0±0.7) g vs. (4.4±1.3) g, P<0.05], lower sucrose water preference[(78.4±5.3)% vs. (64.8±6.4)%, P<0.05]; fewer cross-grid times [(42.0± 9.2) times vs. (29.0±6.8) times, P<0.05], stand-up times [(7.4±1.7) times vs. (3.0±0.7) times, P<0.05]. Compared with UCMS, 4-week drug therapy increased sucrose water [(8.0±1.6) g vs. (10.5±1.3) g, P<0.05], and stand-up times (3.0±0.7) times vs. (5.0±1.4) times, P<0.05]. Conclusion This study showed that UCMs had no significant effect on the blood pressure of SHR rats but made WKY rats and SHR rats have depression-like behavior. Drug treatment can improve the depression-like behavior of SHR rats.