Objective: To study the effect and comparison of ginsenosides Rg1 and Rb1 on depression-like and anxiety-like behavior in chronic unpredictable stress-induced rats by regulating inflammation. Methods: Seventy SPF grade SD male rats were tested for sugar and water preference after 5 days of adaptation. The animals were divided into 7 groups according to the sugar and water preference index, namely blank control group, model group, positive drug group, ginsenoside Rg1 30 μmol/kg dose group, ginsenoside Rg1 60 μmol/kg dose group, ginsenoside Rb1 30 μmol/kg dose group, ginsenoside Rb1 60 μmol/kg dose group. Except for the blank control group, the other rats were randomly subjected to 1-2 different stimulating factors every day for a total of 35 days. On the 36th day, behavioral experiments such as sugar and water preference, open field experiment, novel environment feeding inhibition experiment, elevated cross maze experiment and forced swimming were conducted to investigate its anti-depression and anti-anxiety effects. The serum and hippocampal levels of IL-1β, IL-6, TNF-α and serum corticosterone (CORT) were measured by Elisa. Result: Compared with model group, ginsenoside Rg1 and Rb1treatments significantly increased the sucrose consumption in the sucrose preference test and decrease in immobility in the forced swimming test., the latency to eat in novelty-suppressed feeding test of ginsenoside Rg1 (60 μmol/kg) group was significantly reduced, and percentage of open arm entries and time in elevated plus maze test of ginsenoside Rg1 (30 and 60 μmol/kg) groups was significantly increased. The content of serum corticosterone in ginsenoside Rg1 and Rb1 dose groups was significantly decreased. The levels of serum IL-1β and IL-6 in ginsenoside Rg1 (30 μmol/kg) dose group were significantly decreased, The levels of TNF-α and IL-6 in serum of ginsenoside Rb1 (30 μmol/kg) group were significantly decreased. And the contents of IL-1β, IL-6 and TNF-α in hippocampus of ginsenoside Rg1 and Rb high dose group were significantly decreased. Conclusion: Both ginsenosides can regulate the HPA axis and inhibit neuroinflammation, improving depression and anxieti-like behavior in rats induced by chronic unpredictable stress. In addition, ginsenoside Rg1 has a significantly better anti-anxiety effect than Rb1.