Particle size reduction of talc from micro- to nanoscale gradually enhanced its cytotoxicity however its inflammatory potential is still not explored. In the current study we observed increased TNF-alpha, IL-1beta and IL-6 mRNA levels in macrophages exposed to Nano-Talc (NT). Further, NT particles also showed constituent phosphorylation of both p38 and ERK1/2 pathway however JNK phosphorylation was transient. Pre-treatment of macrophages with p38 and ERK1/2 inhibitors either alone or in combination showed significant reduction in TNF-alpha mRNA stability, clearly suggesting their role in TNF-alpha mRNA stabilization and expression. Our observations clearly demonstrated the inflammatory potential of NT particles which might be at least partial and potential mechanism in talc mediated pathogenecity in the exposed population.