Silicosis is a lung inflammatory disease caused by chronic exposure to crystalline silica (CS). Leukotriene B(4) (LTB(4)) plays an important role in neutrophilic inflammation that drives silicosis and promotes lung cancer. Here, we examined the mechanisms involved in CS-induced inflammatory pathways. Phagocytosis of CS particles is essential for the production of LTB(4) and IL-1β in mouse macrophages, mast cells and neutrophils. Phagosomes enclosing CS particles trigger the assembly of “lipidosome” in the cytoplasm that is likely the primary source of CS-induced LTB(4) production. Activation of JNK pathway is essential for both CS-induced LTB(4) and IL-1β production. Studies with bafilomycin-A1 and NLRP3 deficient mice revealed that LTB(4) synthesis in the lipidosome is independent of inflammasome activation. siRNA knockdown and confocal microscopy studies showed that GTPases Rab5c, Rab40c along with JNK1 are essential for lipidosome formation and LTB(4) production. BI-78D3, a JNK inhibitor abrogated CS-induced neutrophilic inflammation in-vivo in an air pouch model. These results highlight an inflammasome independent and JNK activation dependent lipidosome pathway as a regulator of LTB(4) synthesis and CS-induced sterile inflammation.