Activation of microglial cells have been treated as the main role in the pathogenesis of neuropathic inflammation and neurodegenerative disease, including Parkinson's disease (PD), prion disease and Alzheimer's disease (AD). Resolvin D2 (RvD2) is derived from omega-3 polyunsaturated fatty acid and performs potent anti-inflammatory and pro-resolution effects. Here we investigated the effects of intrathecal injection of RvD2 for substantia nigra pars compacta (SNpc) in vivo' and primary microglia in vitro experiment on pro-inflammatory cytokine expression and NF-KB activation in Lipopolysaccharide (LPS)-induced PD rat model. The total of 30 days experimental period were used for the rats' experiment, the LPS-induced inflamMation in SNpc increase the expression of NO, iNOS, TNF-alpha, IL-1, IL-18, IL-6, IL-1 beta, ROS production, the translocation of NF-kappa B p65, I kappa B alpha, and IKK beta expression in glial cells. After injection of RvD2, the treatment prevented development of behavioral defects and TLR4/NF-kappa B pathway activation. Therefore, we demonstrated a novel role of RvD2 in treatment of rat PD model and LPS activated microglia inflammation. Given the significant potency of RvD2 and well-known side effects of microglia inflammatory inhibitors, it may represent novel hotspot for treating neurodegenerative disease. (C) 2015 Elsevier Inc. All rights reserved.