This trail was conducted to study the effect of L-proline on the growth performance, and blood parameter in the weaned lipopolysaccharide (LPS)-challenged pigs. Thirty six pigs (9.13±0.85 kg) were assigned randomly to dietary treatments in a 2×3 factorial arrangement in a 20-d growth assay. Factors were intraperitoneal injection with saline or LPS, and three dietary L-proline supplement levels (0%, 0.5%, or 1.0%). On d 10, blood samples were collected at 3 h after LPS (100 μg LPS/kg body weight [BW]) or saline injection. On d 20 of the trial, all pigs were orally administrated D-xylose (0.1 g/kg BW) at 2 h, and blood samples were collected at 3 h after LPS or saline injection. As a result, dietary supplementation with 0.5% proline had a tendency to increase average daily gain (ADG) in piglets during d 10 to 20 (p = 0.088). Without LPS challenge, dietary supplementation with 1.0% proline had no effect on growth hormone (GH) concentrations on d 10 (p>0.05), but decreased it after LPS challenge (p<0.05). There was LPS challenge×proline interaction for GH concentrations on d 10 (p<0.05). Dietary supplementation with 1.0% proline decreased glucagon concentration on d 10 after LPS challenge (p<0.05). In addition, dietary supplementation with proline increased superoxide dismutase (SOD) activity significantly on d 10 and 20 (p<0.05), and 1.0% proline increased heat shock proteins-70 concentration on d 10 (p<0.05). Moreover, proline supplementation increased diamine oxidase (DAO) concentrations after LPS challenge (p<0.05). There was LPS challenge×proline interaction for DAO (p<0.05). Furthermore, dietary supplementation with 1.0% proline increased the D-xylose level when no LPS challenge (p<0.05). These results indicate that proline supplementation could improve growth performance, increase SOD activities, and has a positive effect on the gastrointestinal tract digestibility in early weaned pigs.