CD4(+) T cells participate in regulating immune response and inflammation. MiRNA is a type of small noncoding RNA that can regulate gene expression at posttranscriptional level. This study investigated miR-363 expression and the role in CD4(+) T cells from arthritis. CD4(+) T cells were isolated from the synovia of 26 arthritis patients and healthy control using immunomagnetic beads to test miR-363 expression. MiR-363 target gene was predicted by bioinformatics and confirmed by luciferase reporter gene assay. PDPN level in CD4(+) T cells were detected by Western blot. MiR-363 or inhibitor was transfected to change miR-363 expression in Jurkat cells. Cell cycle was evaluated by flow cytometry. PDPN and inflammatory cytokines expressions were tested by Western blot. MiR-363 expression downregulated in CD4(+) T cells from arthritis patients compared with healthy control (P < 0.05). PDPN was jianhgleconfirmed as the target gene of miR-363 by bioinformatics and luciferase reporter gene assay. MiR-363 downregulation in CD4(+) T cells obviously shortened cell cycle, enhanced cell proliferation, promoted PDPN expression, and facilitated inflammatory cytokines release including TNF-alpha and MMP-3 (P < 0.05). MiR-363 expression reduced in CD4(+) T cells from synovia of arthritis patients, thus to enhance CD4(+) T cells proliferation, elevate PDPN expression, and promote inflammatory cytokines release.