Around 25 million people suffer from pesticide poisonings every year in developing countries due to lack of directions for pesticides handling. Fipronil belongs to phenylpyrazole family and has been linked to airway inflammation. Endotoxins also contribute to lung inflammation. There remains strong possibility of co-exposure of fipronil and endotoxins due to ubiquitous nature of endotoxins. Recently HMGB1 signaling has been crucially implicated in many lung pathologies. However, there is no data on role of HMGB1 signaling during fipronil induced lung damage with or without endotoxins. Hence, we employed a comprehensive microarray approach in a mouse model to study the pulmonary immune response profiling influenced by oral administration of fipronil (1/20th of LD50) individually or in combination with intranasal challenge with endotoxin (80µg/mouse). Ingenuity Pathway Analysis (IPA) software analysis predicted HMGB1signaling as key pathway involved in airway inflammation following exposure to fipronil. Fipronil alone did not alter HMGB4 expression. However, there was 2.3 and 5.3 fold increase in HMGB4 expression following exposure to endotoxin alone or in combination with fipronil, respectively. IL17C showed 1.3 fold expression following exposure to endotoxin or fipronil alone and 4.6 fold increase when both were combined. Endotoxin decreased IL4 and MAPK8 expression (0.37 and 0.7 fold). However fipronil resulted 4.2 and 5.0 fold increase in IL4 and MAPK8 expression, respectively. Fipronil also caused 3.4 folds increase in VCAM1, however no change was detected in endotoxin group. Further there was 2.4 fold decrease in VCAM1 expression when fipronil was combined with endotoxin. The microarray expression data are being validated by RT-qPCR analysis for the selected genes. The data put together indicate that fipronil or/and endotoxin induces lung inflammation via HMGB1signaling by altering expression of HMGB4, IL17C, IL4, VCAM1 and MAPK8