We investigated the influence of small- and large-dose capsaicin in modulating systemic inflammatory responses during different stages of sepsis in rats. Rats were divided into six groups: group C, control; group S, sepsis; group CLC, small dose of capsaicin (1 mg/kg subcutaneously); group SLC, small dose of capsaicin plus sepsis; group CHC, large dose of capsaicin (150 mg/kg subcutaneously); group SHC, large dose of capsaicin plus sepsis. Rats were made septic by cecal ligation and puncture (CLP). Each group was subdivided into two subgroups. The animals were killed at 9 or 18 h after CLP. Plasma concentrations of calcitonin gene-related peptide (CGRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and total nitrite/nitrate (NOx) were measured. Superoxide dismutase and malondialdehyde (MDA) were determined in liver, lung, and heart tissues. CGRP was increased in groups S, CLC, and SLC when compared with the other groups. In the SLC group, plasma concentrations of TNF-alpha, IL-6, NOx, and tissue MDA levels were reduced and IL-10 level was increased when compared with groups S and SHC 18 h after CLP (P < 0.05). Small-dose capsaicin treatment increased antiinflammatory IL-10 levels and attenuated the increases in proinflammatory cytokines, NOx, and tissue MDA in septic rats.