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This study was designed to investigate the effect of early thyroxine (T4) treatment on brain-derived neurotrophic factor level during the development of neonatal rat cerebellum.During the first postnatal 10 days (P10),newborn Sprague-Dawley rats were randomly allocated to receive treatment by subcutaneous injection of 0.05 mL 7.5 μg/d L-thyroxine in 0.9% phosphate buffered saline (thyroxine group) or an identical volume of normal saline (control group).At postnatal day 10 (P10),P15 and P30,plasma thyroxine concentration was determined.The distribution and form of brain-derived neurotrophic factor (BDNF)-immunoreactive Purkinje cells and BDNF protein level in the rat cerebellum were investigated via immunohisto-chemical staining and enzyme-linked immunosorbent assay.In addition,BDNF-immunoreactive Purkinje cells at P10 were observed by immunoelectron microscopy.At P10,plasma thyroxine concentration was significantly higher in the thyroxine group than in the control group (P < 0.05).At P 15,plasma thyroxine concentration was significantly decreased in the thyrox-ine group than in the control group (P < 0.05).At P30,there was no significant difference in plasma thyroxine concentration between the thyroxine and control groups (P > 0.05).A similar developmental pattern of BDNF-immunoreactive Purkinje cells was observed in both thyroxine and control groups at all ages,however,the number of BDNF-immunoreactive Pur-kinje cells was significantly greater in the thyroxine group than in the control group at P10 (P < 0.05).The level of BDNF protein was significantly higher in the thyroxine group than in the control group at P10 and P15,however,no difference in BDNF protein level was found between both groups at P30.At P 10,numerous mitochondria and cytoplasm exhibited short segments of rough endoplasmic reticulum in a matrix of free ribsomes.Numerous short segments of endoplasmic reticu-lum showed a tendency of parallel alignment.Electron microscopic observations of BDNF-immunoreactive Purkinje cells revealed numerous short segments of rough endoplasmic reticulum,many of which showed a tendency of more parallel alignment in the thyroxine group than in the control group.Our results indicate that the increases in BDNF protein level and BDNF-immunoreactive Purkinje cell number after early postnatal thyroxine treatment are transient during early postnatal life,and these alterations are not kept until adolescence.