Idiopathic Pulmonary Fibrosis (IPF) is a chronic disease characterized by the accumulation of fibrotic tissue in the lung. This accumulation results from a dysfunction in the healing process; but, the exact mechanisms that lead to this trouble are still poorly understood. Different experimental models of the disease exist, such as radiation damage, instillation of silica or asbestos and transgenic mice or gene transfer employing fibrogenic cytokines. However, the most frequently used model is the intratracheal (IT) instillation of bleomycin in rodent. In the present studies, we compared instillation and aerosolization of this fibrotic agent. 47 Wistar rats received 3IU of bleomycin intratracheally, either by instillation (22) or by spraying (25). Manipulated animals and shams were sacrificed at day 3, 7, 14, 21 and 56 and the presence and intensity of the fibrotic process were studied histologically. Therefore, slides were obtained from each pulmonary lobes and a trichrome blue staining was performed. Fibrosis was then quantified using a modified Ashcroft scale (grade 0 to 8). When fields from the most affected part of the each lobe were considered, the value obtained was on average 0.6±0.1 in shams, and 1.8±0.1, 1.9±0.4, 2.7±0.3, 2.8±0.5, 3.2±0.4 in the instillation group at day 3, 7, 14, 21 and 56 respectively. Corresponding values after aerosolization were 1.4±0.1, 1.9±0.2, 3.8±0.1, 4.1±0.2, 4.6±0.3. In contrast, when the mean value of randomly chosen fields in the six lobes were considered, the corresponding results were 0.6±0.1 in shams and 0.7±0.1, 0.3±0.1, 0.9±0.1, 0.6±0.1, 0.9±0.1 and 0.5±0.1, 0.5±0.1, 1.5±0.3, 1.8±0.4, 2.3±0.2 with instillation and spraying respectively (same times). Interobserver variability was also studied. In conclusions, both instillation and aerosolization of bleomycin induce the development of fibrosis as demonstrated by the same progression of the highest modified Ashcroft score. Aerosolization, however, allows a homogeneous distribution of lesions among the lungs as demonstrated by the persistence of a time effect when random sampling is considered for the analysis.