A rubber composition including guayule rubber and 15 to 90 phr silica. The rubber can be cis-1,4 polyisoprene and include 15 to 90 phr silica and contain less than 20% of the proteins associated with Hevea rubber and further include at least a trace of resins present in other natural rubbers. The rubber can be cis-1,4 polyisoprene and further include between at least a trace and 3% by weight of resins present in guayule rubber. The rubber composition can further be comprised of a synthetic rubber and include between about 40-100 phr of guayule rubber, and silica. The silica can be hydrophobated.