Effect of exposure to diesel exhaust (DE) for different durations was evaluated using histopathological and biochemical parameters in respiratory system of the rats. Animals were exposed to 1 part DE diluted with 5 parts of clean air in a simulation chamber for 15 min/day for 1, 7, 14 and 21 days. After completion of various exposures, biochemical parameters including elastase inhibitory capacity (EIC) and protein content of the bronchial airway lavage (BAL) and histopathological changes along with lung/body weight ratio were assessed. The elastase inhibitory capacity (an index of the protection against destruction of elastin, a lung connective tissue) was maximum at 1 week indicating thereby that the body renders protection against injury by increasing EIC levels in the initial phase. However, protein content in the BALF increased after 1 week and reached maximum at 2 weeks. Histopathological changes followed similar time course of pattern with accumulation of macrophages and protein exudation. Prolonged exposure up to 3 weeks, however was accompanied by chronic inflammatory changes and thickening of alveolar septa and blood vessels. Changes in lung/body weight ratio and suspended particulate matter (SPM) deposited on filters (simulation chamber) correlated well with EIC, protein content in BALF and histopathological changes. The biochemical findings accompanied with chronic structural changes in the lungs of rats following exposure to DE could be relevant to the clinical observation of increased incidence of chronic lung diseases after continued DE exposure.