Objective: To observe the effects of apocynum venetum leaves extract(AVLE) on anxiety-like behavior caused by chronic restraint stress(CRS). Methods: Male C57BL/6 mice were randomly divided into 4 groups, 5 per group: control group(equivalent physiological saline 0.2 ml/10 g), CRS model group(equivalent physiological saline 0.2 ml/10 g), AVLE treatment group(AVLE 120 mg/kg) and positive control group(paroxetine hydrochloride 3 mg/kg). The anxiety mouse model of chronic restraint stress was established, and the anxiety level of mice treated with apocynum venetum leaf extract was evaluated by open field test and elevated cross maze test. Immunofluorescence staining was used to detect the changes of serotonin receptor in hypothalamic paraventricular nucleus. Chemogenetics combined with adeno-associated virus was used to detect the effect of hypothalamic oxytocin neurons on the anxiety regulation of AVLE. Results: Compared with the model group, apocynum venetum leaves extract could increase the total distance of open field exercise, the activity time, the time of mice entering the central area(P<0.05), and the activity distance and time of mouse elevated maze(P<0.05). The expression of serotonin 1A receptor in the paraventricular nucleus of hypothalamus was enhanced after treatment with AVLE, and inhibition of serotonin 1A receptor and oxytocin neurons in hypothalamic paraventricular nucleus could decrease activity level in mice(P<0.05). Conclusion AVLE can improve the anxiety state and activity ability of CRS mice, and its effect is related to serotonin receptor and oxytocin neurons in hypothalamic paraventricular nucleus.