Five inspectors from the International Atomic Energy Agency (IAEA) aboard a van loaded with equipment arrived at the Korean Atomic Energy Research Institute in the central city of Daejon, 160 kilometers (100 miles) south of Seoul, witnesses said.
The state institute remained tight-lipped about the inspection and denied reporters access to its facilities.
Earlier this month as a first team of IAEA inspectors was visiting South Korea, the government revealed that its scientists secretly enriched a small amount of uranium in 2000. Then came revelations that scientists had extracted a tiny amount of plutonium in 1982.
South Korea insisted the lab experiments were not linked to nuclear weapons programs. IAEA chief Mohamed ElBaradei, however, has expressed "serious concern" about the activities.
The new inspection team would report back to the Vienna-based IAEA by November after interviewing scientists involved in nuclear experiments.
On Saturday South Korea made a fresh pledge that it would not develop or possess nuclear weapons but would pursue scientific atomic research transparently.
The case, however, has already damaged multinational efforts to persuade Stalinist North Korea to give up its nuclear weapons programs.
Pyongyang's official KCNA news agency warned Saturday that the communist country would not abandon its nuclear ambitions. It also said North Korea would not attend multilateral talks on its nuclear program unless South Korea clears up suspicions over its nuclear experiments.
"South Korea's secret nuclear activities are an inevitable outcome of the US double standard policy on the Korean Peninsula nuclear problems," the North's ruling party newspaper, Rodong Sinmun, said Monday in an editorial carried by South Korea's Yonhap news agency.
"Under such circumstances, (North Korea) will never abandon its nuclear weapons programs."
South Korea said its scientists produced 150 kilograms (330 pounds) of uranium metal in 1982 in undeclared activities and a small amount of this was used in 2000 to produce the enriched uranium.
They also admitted to having extracted a miniscule amount of plutonium from 2.5 kilograms of fuel rods in secret research in 1982.
South Korea has the world's sixth-largest civilian nuclear industry, operating 19 nuclear power plants that produce 40 percent of the country's energy needs.