Amid colourful and sometimes tense scenes Gaddafi shook hands with European Commission chief Romano Prodi as he arrived at the headquarters of the EU executive for the two-day visit.
His team of female bodyguards was put to its first test as crowds of demonstrators, mostly supporting him but including some human rights protestors, swirled around the entrance to the commission in Brussels' EU district.
At one point a bodyguard leapt in to bundle a camera assistant out of the way of Gaddafi, who flashed a V-sign as he stood in front of the Libyan and EU flags next to Prodi, who was dressed in a smart blue suit.
The trip comes days after US President George W Bush's announcement that Washington was easing nearly two decades of economic sanctions on the oil-rich country.
First official trip
It's Gaddafi's first official trip outside Africa or the Middle East since 1989 and marks the latest step of his country's return to international acceptability, which accelerated last December with an announcement that Libya was abandoning efforts to obtain weapons of mass destruction.
On the agenda is likely to be the arms embargo that remains in force against Libya despite the lifting of other international sanctions, and boosting Tripoli's relationship with the European Union.
But the visit is not without clouds. On the eve of his trip Amnesty International said Tripoli still regularly flouted human rights, charging that there was a "climate of fear" in Libya.
After arriving at a private airfield outside Brussels, Gaddafi headed for talks with Prodi before lunch with the European commissioners. In the evening he was due to dine with Belgian Prime Minister Guy Verhofstadt.
"He has worked relentlessly on this issue since the beginning of his mandate... and is looking forward to the visit," said Prodi's spokesperson Reijo Kemppinenn.
The European Union is under pressure to lift its arms embargo against Libya, with Italy in particular pressing for the bloc to offer more help to the north African country in the fight against illegal immigration.
With Libya one of the jumping-off points for hazardous - and often deadly - clandestine crossings by boatloads of illegal migrants heading to Europe, Italy wants to be able to sell the country equipment such as helicopters, radar and night-vision goggles.
The Brussels talks are set to discuss Libya's entry into the Euromed partnership, a political and security agreement between the EU and the Mediterranean rim countries of North Africa. Libya remains the only country in the region that has no formal relations with the EU.