Agricultural pest insects have been controlled primarily through the use of chemical insecticides. Bacillus thuringiensis (Bt) bacterium is an alternative for biological control since it synthesizes entomopathogenic protoxins which are codified by different cry genes. This study evaluated the insecticidal activity and the histopathological effects of bacterial suspension and purified Cry1Ba protein from B. thuringiensis thuringiensis strain 4412 in the midgut epithelial cells of S. frugiperda larvae. To accomplish that, bioassays were done with bacteriological suspension of the Bt strain, which was applied to the Poitout diet, and the toxicity of this strain was also determined by the LC50, using purified protein, where the diet was substituted by disks of corn leaf. In the control group the protein and bacterial culture were replaced by sterile distilled water. S. frugiperda larvae of 2nd instar were prepared through the inclusion paraffin techniques to evaluate the histopathology. Our results showed that the tested B. thuringiensis thuringiensis 4412, was highly toxic in the bioassays with 100% of corrected mortality to S. frugiperda larvae. In addition, the LC50 results indicated that the expressed Cry1Ba protein was toxic too, with a LC50 of 10.88 μg/ml. The histopathological analysis of S. frugiperda midgut showed a progressive loss of epithelial cell definition after 3h, in both treatments. At 24h post treatment, their midgut changes included vacuolization of the cytoplasm, hypertrophy of the epithelial cells, and vesicle formation in the apical region of both goblet and columnar cells. Also, the brush border membrane was damaged, especially in goblet cells.