Sambucus nigra (S. nigra) is widely distributed in Europe, Asia, and North America; the plant has been used in folk medicine for centuries. Toll-like receptors (TLR) are transmembrane proteins found in various cells. Interleukin-4 (IL-4) is a pleiotropic cytokine that regulates cellular proliferation, and gene expression in various cell types. This study aimed to investigate the immunohistochemical expression of TLR4 and IL-4 in the lungs of healthy and diabetic rats treated with S. nigra. Rats were randomly divided into four groups (control, S. nigra, diabetes, diabetes + S. niga), each containing eight rats. When the groups were generally evaluated, there was no significant difference in the control group, S. nigra group, and diabetes + S. nigra group. However, an increase in TLR4 immunoreaction intensity was determined in the lungs of diabetic rats. It was observed that IL-4 immunopositive cells were significantly lower in the diabetes group compared to the other groups but increased in the S. nigra group. S. nigra was found to increase the decreased IL-4 expression in the diabetes group compared to the control group. With the findings we obtained in our study, we observed that S. nigra could positively affect the immune system and be effective in metabolic disorders such as diabetes.