Effective protection against pathogenic bacteria requires both mucosal and systemic immune responses. Intranasal administration of antigens induces these responses. The protective effect of intranasal immunization with different formalin-inactivated bacterial lysates in albino mice was evaluated. This study used formalin inactivated lysate of each of the following Escherichia coli , Pseudomonas aeroginosa ,Salmonella typhi , Shigella flexeneri , Staphylococcus aureus , Bacillus subtilis and mixed bacterial lysates. The lysate was administered intranasally (5μl/ nostril) once daily for seven consecutive days. The results of this study recorded some changes in peripheral blood total and differential leucocytic counts , peritoneal fluid and bone marrow lymphocytic percentages . Spleen and thymus weight changes were reported under the effect of Salmonella typhi lysate, Shigella flexeneri lysate and Staph. aureus lysate. The level of immunoglobulin G (Ig G) was assessed in serum, bronchial lavage and nasal bed harvest. The levels of Ig G were significantly elevated in the three determinants, suggesting an efficient immunostimulatory effect of bacterial lysates. Some of these levels were exceeding 2-3 folds of that of the control group. Histopathological studies recorded changes in some reticuloendothelial system organs including the liver, spleen and thymus gland, besides, some changes were also observed in the lung and bronchi under the effect of intranasal vaccination. This study supports the immunoprotective effect of intranasal vaccination, using bacterial lysates.