Objective(s): This research aimed to investigate the effect of ۲ types of exercise on apoptosis, neurogenesis, and angiogenesis factors in the penumbra area of stroke during the rehabilitation period after stroke. Materials and Methods: A transient distal middle cerebral artery occlusion (td-MCAO) model was used to induce stroke and after that, the animals were randomly divided into three groups: stroke, stroke + continuous exercise with increasing duration (CTID), and stroke + exercise with increasing intensity (CTII). At ۲۴ hr spost-stroke , MRA, neurological deficit, and behavioral tests were conducted, and also continuous exercises were conducted for five consecutive days, Finally, MRI and behavioral tests were performed, and ۲۴ hr after that, tissue separation and blood sampling were performed to evaluate plasma irisin, Extracellular Signal-Regulated Kinases ۱ and ۲ (ERK۱/۲) / cAMP Response Element-Binding Protein (CREB) / ۹۰ kDa Ribosomal S۶ Kinase (P۹۰RSK) pathway, Vascular Endothelial Growth Factor (VEGF) / Vascular Endothelial Growth Factor Receptor ۲ (VEGF-R۲), and Brain-Derived Neurotrophic Factor (BDNF) / Tropomyosin Receptor Kinase B (TrKB) levels. for statistical analysis, one-way and two-way ANOVA tests were used at the significance level of P<۰.۰۵.Results: Both training models reduced the volume of stroke and neurological defects compared to the stroke group (P<۰.۰۵), while the amounts of irisin and CREB in the CTID group increased significantly compared to the CTII and stroke groups (P<۰.۰۱). VEGFR۲ values in training groups increased significantly compared to the stroke group (P<۰.۰۵) but in the CTII group, VEGFR۲ values increased significantly compared to the CTID group (P<۰.۰۵).Conclusion: The findings of the present study showed it seems that doing exercises with moderate intensities and gradually increasing the duration of exercise in the acute phase after stroke can be considered a suitable treatment in future research.