Rauwolfia serpentina is effectual in the treatment of hypertension as well as in psychotic diseases like anxiety, schizophrenia, insanity, insomnia etc. Roots of Rauwolfia serpentina plant have various biological activities due to isolation of different indole alkaloids and associated constituents from it. The principle alkaloid of Rauwolfia serpentina is reserpine. In this study neuroprotective effects of Rauwolfia serpentina plant extract following the exposure to acute immobilization (2h) stress in rats were investigated. The extract of the plant administered orally at non-sedative dose 30mg/kg before immobilization (2h) to observe stress induced behavioral deficits. Neuroprotective efficacy of extract was assessed in terms of alteration in activities of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT). We also monitored leptin, corticosterone and glucose levels in plasma to obtain an imminent role of Rauwolfia serpentina. Twenty four animals randomly assigned into two equal groups (12 in each group) i.e. test and control. Test animals were orally administered with Rauwolfia serpentina (30mg/kg) while controls receive saline (1ml/kg). Each group was subdivided into stressed and unstressed groups. Behavioral deficits were monitored in the open field and light dark activity box. Animals were decapitated; plasma samples were collected for CAT, SOD, corticosterone, leptin and glucose estimation. Orally administered Rauwolfia serpentina attenuates stress induced behavioral deficits and rise antioxidant enzymes levels. Plant extract also prevents the stress-induced increase in corticosterone but glucose levels do not manifest any significant change. Immobilization stress (2h) induced decrease of plasma leptin levels were reversed by Rauwolfia serpentina. Therefore, the present study suggests that Rauwolfia serpentina has potentiality to antagonize undesirable effects of immobilization stress (2h) by reducing stress perception and inhibitory effects of stress on the activity of hypothalamic pituitary adrenal (HPA) axis and animal behaviors. Despite an apparent role of Rauwolfia serpentina the mechanism of action at molecular level causing the acute anxiolytic effects of oral administration of plant extract remains to be determined.