This study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarization and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to 3 groups: normal control fed with AIN-93G diet, and 2 sepsis groups provided with either AIN-93G-based diet or identical components except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with cecal ligation and puncture and were sacrificed at 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas interleukin (IL)-4-, and Foxp3-expressing CD4+ T cells percentages were upregulated. Compared to the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells, reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker Kim-1 were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more-balanced blood T helper cell polarization, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects in risk of abdominal infection.