Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. $PGE_2$ modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of $PGE_2$ in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether $PGE_2$ mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL $PGE_2$ and LPS-stimulated production of $PGE_2$ by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous $PGE_2$ enhanced production of IL-6, IL-10, and NO but decreased $TNF-{alpha}$ by macrophages and augmented $IFN-{gamma}$, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous $PGE_2$ also enhanced production of $IFN-{gamma}$, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a $PGE_2$ synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced $TNF-{alpha}$. Indo remarkably inhibited Con A-increased production of $IFN-{gamma}$, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous $PGE_2$ may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and $IFN-{gamma}$, and NO in pristane-induced lupus mice.