Lindane is very commonly used organochlorine pesticide and has been reported to cause several toxic effects including respiratory insufficiency. However, effects of low concentration of lindane alone or in combination with microbial molecules on lungs are not fully understood. To understand the effects a preliminary study was designed on Swiss albino mouse. Male mice were divided into treatment and control group (20; each). Treatment mice were given lindane in ground nut oil orally at 0.25 mg kg−1 day−1 for 60 days. After treatment, 10 mice were challenged with intranasal Escherichia coli lipopolysaccharide (LPS; 80 μg per mice) and remaining 10 with normal saline. The mice were euthanized 16 h post-LPS exposure. Control mice (10 each) were given normal saline or the LPS alone. Mice exposed with lindane and in combination with LPS had increase in total cell counts and leukocyte counts in broncho-alveolar lavage. Histological examination showed lung injury in the lindane-treated mice. The histopathological changes were more pronounced in lindane along with LPS-exposed mice. Lindane alone and in combination with LPS showed expression of immunopositive Toll-like receptor (TLR)-4 and tumour necrosis factor-alpha (TNF-α) positive reaction in various cells of lungs. While LPS induced acute inflammation in the lungs, combination of lindane and LPS exacerbated histological signs of the inflammation. The data indicate that lindane alone or in combination with LPS caused changes in lung morphology and altered TLR-4 and TNF-α expression which may have led to altered response to LPS challenge.