Levisticum officinale (Apiaceae) has been identified as a medicinal plant in traditional medicine, with the anti-inflammatory, antioxidant, and anticholinesterase activities. The present study aims to evaluate the effects of Levisticum officinale extract (LOE) on lipopolysaccharide (LPS)-induced learning and memory deficits and to examine its potential mechanisms. LOE was administered to adult male Wistar rats at doses of 100, 200, and 400 mg kg-1 for a week. Later, LPS was intraperitoneally injected at a dose of 1 mg kg-1 to induce neuroinflammation, and treatment with LOE continued for 3 more weeks. Behavioral, biochemical, and molecular analyses were performed at the end of the experiment. Moreover, quantitative immunohistochemical assessments of the expression of Ki-67 (intracellular proliferation marker) in the hippocampus were performed. The results revealed that LPS injection caused spatial memory impairment in the rats. Daily LOE treatment at applied doses for 4 weeks attenuated spatial learning and memory deficits in LPS-injected rats. Furthermore, LPS significantly increased the mRNA expression level of interleukin-6 in the hippocampus, which was accompanied by decreased brain-derived neurotrophic factor (BDNF) mRNA expression levels. Moreover, LPS increased the levels of malondialdehyde, reduced the antioxidant enzyme activities of catalase and superoxide dismutase in the hippocampus, and impaired neurogenesis. However, pre-treatment with LOE at a dose of 100 mg kg-1 significantly reversed the LPS-induced changes, and improved neurogenesis. In conclusion, the beneficial effect of LOE on the improvement of learning and memory could be attributed to its anti-inflammatory and antioxidant activities, along with its ability to increase BDNF expression and neurogenesis in the hippocampus.