The objective of this study was to compare the effects of natural and synthetic chemical pesticides, thereby examining the supposed selectivity of these natural compounds on Apis mellifera bees. The LC50 values used in the bioassays were obtained from the research by Souza et al. (2023) and are as follows: Karate® (13.4 µL/100 mL), Limonene compound (1,440 µL/100 mL), and Roundup® (712,290 µL/100 mL). However, as reported by these authors, a concentration of 250 µL/100 ml was used for Azamax®. These LC50 values, along with a concentration of 250 µL/100 mL of Azamax®, were employed in immunohistochemical analyzes using the TUNEL method and PCNA in the midgut of bees. Immunological assessments (nitric oxide, phenoloxidase, and oxidative stress markers TBARS and GSH) were also conducted on adult worker bees. The xenobiotic treatments did not reveal apoptosis or cell proliferation. Nonetheless, we observed epithelial degeneration, marked by the presence of vacuolated cells, suggesting a necrotic process. Except for the Limonene compound, all substances induced oxidative stress, leading to increased levels of TBARS. Although there were no differences in GSH levels, we observed alterations in the immune system of these insects, characterized by increased phenoloxidase activity and NO2 levels. Based on the acquired results, it is possible to conclude that caution should be exercised when using chemical pesticides in agriculture, whether they are of synthetic or natural origin, as they have the potential to cause irreversible histopathological and immunological damage. This study also underscores the importance of conducting more comprehensive investigations into the impact of natural products on the physiology of pollinator insects.