This study investigates the anti-inflammatory effects of ibrutinib in microglia inflammation induced by lipopolysaccharide (LPS) .To investigate the effects of ibrutinib on oxidative stress and inflammation in mouse microglial C8-B4 cell line, cells were treated with ibrutinib (1 and 10 μM) or vehicle (1% DMSO) for 1 h, followed by 1 μg/ml LPS or PBS in case of the control samples, for 23 h. Intracellular ROS was measured by using fluorescence microscopy using 2′,7′-dihydrofluorescein diacetate dye (DCFH-DA). Inflammatory mediator levels (NF kappa beta, TLR4, TNFalpha), and anti-inflammatory cytokine IL10 were measured by western blot. Moreover, senescence levels of cells were measured by checking beta gal formation in cells and cell migration by using scratch wound migration assay. The LPS-induced elevation of intracellular ROS levels was reduced after ibrutinib treatment. Ibrutinib suppressed the nuclear translocation of NF kappa beta and reduced levels of inflammatory mediators tumor necrosis factor TNF-alpha, toll like receptor (TLR)-4, interleukin (IL)-10. Also, ibrutinib significantly decreased LPS-induced senescence levels in cells and prevented cells migration as well. Altogether, these results suggest that ibrutinib decrease ROS-induced oxidative stress and inflammation by suppressing NF kappa beta/TNF alpha production.In conclusion, our results reveal that ibrutinib inhibits oxidative stress by inhibiting NF-κB signalling pathway. Thus, ibrutinib could be a potential therapeutic agent for neurodegenerative diseases associated with inflammation and oxidative stress.Fig. 1(A&B): Effect of ibrutinib and LPS on intracellular ROS in C8-B4 microglia.