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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by interleukin (IL)-6 and IL-10 that generate nearly opposing responses. The suppressor of cytokine signaling 3 (SOCS3) is the negative regulator of STAT3 and plays an important role in the negative regulation of the inflammatory process. Evidence has shown the importance of STAT3 and SOCS3 during implantation and normal pregnancy. However, little is known about the relationship of both factors under hyperglycemic condition. The aim of this study was to evaluate the placenta regions exhibiting immunopositivity for STAT3 and SOCS3 in hyperglycemic rats, as well as correlate these proteins with IL-10 and IL-6 levels. It was observed increased expression of STAT3 at the labyrinth (approximately 47% of increase compared to control) and junctional zone (approximately 32% of increase compared to control) from hyperglycemic placentas. Similar results were observed to SOCS3 (approximately 71% -labyrinth- and 53% -junctional zone- of increase compared to control). The levels of IL-10 were augmented at hyperglycemic placentas (approximately 1.5 fold of increase) and they were positively correlated with the increase of STAT3 at the labyrinth and SOCS at junctional zone. Therefore, under hyperglycemic conditions, the relation between STAT3 and SOCS3 was changed, leading to unbalance of the cytokine profile.