The underlying mechanisms of Alzheimer's Disease (AD) are still unclear. It is suggested that poly(ADP-ribose) polymerase-1(PARP-1) overactivation can cause neuroinflammation and cell death. In this study we searched the effects of nicotinamide(NA), endogenous PARP-1 inhibitor, on oxidative stress, apoptosis, and the regulation of PARP-1 and nuclear factor kappa B(NF-kappa B) in amyloid beta peptide(1-42)(A beta(1-42))-induced neurodegeneration. Sprague-Dawley rats were divided into four groups as control, A beta(1-42), A beta(1-42) + NA(100 and 500 mg/kg). All groups were stereotaxically injected bilaterally into the hippocampus with A beta(1-42) or saline. After surgery NA administrations were made intraperitoneally(ip) for 7 days. In order to investigate the effects of A beta(1-42) and NA, protein carbonyls, lipid peroxidation, reactive oxygen species(ROS) production, glutathione(GSH) levels, activities of antioxidant enzymes(catalase, superoxide dismutase, glutathione peroxidase), mitochondrial function, mRNA and protein levels of PARP-1, NF-kappa B, p53, Bax, and Bcl-2 were measured in specific brain regions such as cortex and hippocampus. A beta(1-42) treatment only increased the oxidative stress parameters and caused decline in antioxidant enzyme activities, mitochondrial function, and GSH levels. Also, overexpression of PARP-1, NF-kappa B, p53, Bax, and the decreased levels of Bcl-2 were observed in A beta(1-42)-treated group. NA treatments against A beta(1-42)-upregulated Bcl-2 and downregulated PARP-1, NF-kappa B, p53, and Bax levels. NA treatments also decreased the oxidative stress parameters and elevated antioxidant enzyme activities, GSH levels, and mitochondrial function against A beta(1-42) treatment. These data suggest that NA may have a therapeutic potential in neurodegenerative processes due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activity.