Abstract: Objective To explore the pathogenic role of changes of Wnt/β-catenin signaling pathway in the hippocampus in depression- and anxiety-like behaviors caused by prenatal stress (PS) in offspring rats. Methods Twelve female Sprague- Dawley rats weighing 240-260 g were randomly divided into control and restraint stress groups. The rats in the control group received no interventions, and those in restraint stress group were subjected to restraint stress (three times a day, 45 min each time) at the gestational age of 14-20 days. The 1-month-old offspring rats underwent open field test and forced swimming test to assess the anxiety- and depression-like behaviors, and the expressions of Wnt1, Gsk-3β and β-catenin in the hippocampus were detected using Western blotting. Results In open field test, the offspring rats with PS showed significantly decreased crossings of the center (P<0.01) with reduced time spent in the center (P<0.05) compared with control offspring rats. In forced swimming test, the offspring rats in PS group exhibited a significantly longer immobility time than in the control rats, and showed obvious depression- and anxiety-like behaviors. Compared with those in the control offspring rats, Gsk-3β expression increased significantly while the expressions of β-catenin and Wnt1 were significantly lowered in the hippocampus of the offspring rats in PS group (P<0.01). Conclusion PS causes changes in Wnt/β-catenin signaling pathway in the hippocampus to contribute to the occurrence of depression- and anxiety-like behaviors in rats.