Abstract: In order to study the microstructure variation and main element contents in midribs of moldy and rotten tobacco leaves, the middle leaves of cv. Yunyan 85 were taken as the experimental material, scanning electron microscopy was used to observe the midribs of fresh leaves and leaves mildewed and rotted during flue-curing. Energy dispersive spectrometer was used to detect the contents of Na, O, C, Ca and P in midribs and crystals of tobacco leaves. The results showed that tobacco leaves rotted earlier and spread faster than leaves mildewed. The rot and mildew of tobacco leaf appeared in its midrib first, and then extended to both sides of the midrib. When tobacco leaves rotted, their midribs produced calcium oxalate crystal sands which contained a large amount of Ca (30.34%) to accelerate the mildew of tobacco leaves and some P (24.92%) to regulate crystal morphology. Cell bottom wall, cell sidewall and calcium oxalate crystal sands contained Na, O and Ca, cell bottom wall and cell sidewall contained C, and cell sidewall and calcium oxalate crystal sands contained P. The contents of Ca and P in calcium oxalate crystal sands were the highest. The mildew and rot of tobacco leaves mainly occurred on the midrib of leaf base. Rotten tobacco leaves produced calcium oxalate crystal sands, which accelerated the mildew of tobacco leaves.