INTRODUCTION: The parasites undergo morphological and physiological changes that increase their metabolism and temporal protein expression. Those processes induce a state of oxidative stress (OxS) and Plasmodium parasites are highly susceptible to OxS, so redox homeostasis is vital to continue their development. In addition, trafficking of proteins provokes overload in the endoplasmic reticulum (ER) that triggers an adaptive response. In mammals, the activation of the PERK pathway, induces an antioxidant response and phosphorylation of the translation initiation factor eIF2α (P-eIF2α).  P-eIF2α has been reported in the differentiation of other Apicomplexa. METHODS: In this work, we evaluated P. berghei response to protein overload during its diferentiation from gametocytes to ookinetes. RESULTS: During its diferentation, we observed an oscillating pattern in the activation of the system redox and P-eIF2α in mature ookinetes. CONCLUSIONS: These results suggest that P. berghei has mechanisms of adaptive response induced by the accumulation of proteins during sexual differentiation. The study of molecular processes during invasion of the mosquito midgut could provide information to identify potential therapeutic targets.