After flying from Blacksburg, VA to Monroe, NC, the pilot took off on a return flight to Blacksburg without refueling. The pilot stated that before takeoff, he took the fuel tank caps off to visually check the fuel. However, he did not use the dip stick that was provided by the operator to determine the fuel remaining. He estimated that well over half of the total usable supply was remaining, enough for the trip plus a reserve. While en route, he deviated left and right of course and climbed and descended to avoid weather. Also, he used a rich mixture for part of the flight. The fuel gauges began indicating low, but he thought they were inaccurate. During a descent near his destination, the engine lost power. While landing on a highway, he S-turned on final approach to stay behind vehicles. The plane touched down at an angle to the highway, straddled a guard rail, and hit a tree. No fuel was found in the aircraft. The pilot thought he could fly 4 hrs without refueling, but only flew 3.3 to 3.5 hrs.