The present study was conducted to evaluate the immune-enhancing effects of dietary l-glutamine supplementation in porcine circovirus type 2 (PCV2)-infected mice, and to examine the clearance effects of glutamine against PCV2 in experimentally infected mice. A total of sixty Kunming female mice were infected with PCV2 at a dose of 100 TCID50 (50 % tissue culture infection dose) by intraperitoneal injection after 2 weeks of dietary l-glutamine supplementation or l-alanine supplementation (as the control (isonitrogenous) group). The measured variables on 3rd, 5th, 7th, 9th and 11th d post-infection (dpi) included: (1) PCV2 virus loaded in the liver, spleen, heart, lung, kidney, ovary and serum was determined by real-time PCR; (2) IL-2, IL-6, IL-10, interferon (IFN)-α, IFN-γ and C-reactive protein levels in serum were measured by ELISA; (3) serum total superoxide dismutase activity was measured spectrophotometrically at 550 nm absorbance. Dietary l-glutamine supplementation significantly increased serum IL-2 levels on the 3rd (P< 0·01), 5th (P< 0·01), 7th (P< 0·05) and 9th dpi, significantly (P< 0·05) increased serum IL-6 levels on 3rd dpi, significantly (P< 0·05) increased serum IFN-γ levels on the 9th and 11th dpi and significantly decreased (P< 0·01) serum IL-10 levels on the 9th and 11th dpi, compared with those in the control group. Meanwhile, the PCV2 virus genome was detected sporadically throughout the experimental period in both groups. Taken together, the present results suggest that dietary l-glutamine supplementation enhances immune function in PCV2-infected mice.