The therapeutic application of scorpion venom (SV), has been used in traditional medicine. SV contains a variety of peptides that can treat variety of diseases, such as arthritis, rheumatism, pain, cancerous tumors, and skin diseases. Methotrexate (MTX) is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body. MTX is used to treat moderate to severe osteoarthritis, rheumatoid arthritis, gouty arthritis, or ankylosing spondylitis. MTX is also used to treat shoulder pain caused by bursitis or tendinitis. Histological observations showed that diseased groups have edematous, thickened, and hyperplastic synovium membrane with reduction in joint space and empty lacunae appeared. On the other hand, scorpion venom high dose and Methotrexate caused reduction in size of synovium and regression of its inflammatory cell infiltrate with lacunae occupied appeared.