We report on the pneumatocyte structure and function of mouse lung specimens exposed in vitro to two calcined mesoporous silica particles, MCM41-cal (spheres, ∼300 to 1000 nm in diameter) and SBA15-cal (irregular rods averaging ∼500 nm in diameter and ∼1000 nm in length). These mesoporous silica particles are in consideration for potential medical application as delivery vehicles for genes, drugs, and bio-imagers. In the study, lung specimens (about 10 mg each) were excised from male Balb/c mice, immediately immersed in Krebs-Henseleit buffer, ice-cold, and continuously gassed with O(2):CO(2) (95:5). The samples were incubated at 37°C in the same buffer with and without 200 μg/mL MCM41-cal or SBA15-cal for 5-14 h. The tissues were then rinsed thoroughly and processed for light and electron microscopy. Normal alveolar morphology was evident in all the studied specimens. There was no significant difference in the number of apoptotic cells between the treated and untreated samples. Despite their relatively large sizes, the particles were abundantly present in pneumocytes, macrophages, endothelial cells, fibroblasts, and interstitium. They were seen in different areas of the cytoplasm, suggesting intracellular movements. Their presence did not appear to disturb cellular configuration or micro-organelles. Due to their rigidity and surface charges, some were firmly attached to (indenting) the nuclear membrane. The rate of respiration (cellular mitochondrial O(2) consumption, in μM O(2)/min/mg) in specimens exposed to 200 μg/mL particles for up to 12 h was the same as untreated specimens. These findings confirm "reasonable" bioavailability and biocompatibility of calcined mesoporous silicas with mouse lung within at least 5-14 h of exposure time.