The chairman of Japanese conglomerate Hitachi was warned that the "cold economic reality of Brexit" would mean jobs being lost and investment being held back.
Hiroaki Nakanishi said the UK was attractive as the "best base" for accessing the European Union's market of 500 million consumers.
But the chairman of the sprawling business empire, which has invested £50million in Wearside and has a train manufacturing plant in Newton Aycliffe, as well as its global rail HQ in London, said Brexit represented a "boulder on the line".
Vantec, which is part of Hitachi, officially opened its latest investment in Wearside last month, bringing Vantec and Hitachi Transport System’s investment in Sunderland to almost £50million since 2012
Writing in the Daily Mirror Nakanishi warned of the impact of Brexit on Japanese investors: "In the 80s Nissan and Toyota came to the UK on the basis that if they produced here and employed a British workforce they would be treated as European companies.
"This was only possible because Britain was inside the EU; and so the UK car industry was revived and became an exporter again.
"From Japan, this incredible success story looks like a huge gain from the UK's membership of the EU.
"We worry because those advocating Brexit have no answer to how the UK could negotiate cost-free access to this huge market from a position outside it.
"It would take a long time and result in uncertain market conditions; during this renegotiation period, investors would probably be waiting to see the outcomes, hold back on investment, and jobs would be lost.
"This is the cold economic reality of Brexit."
He continued: "Brexit would force us and similar companies to rethink, because we still have a European vision, and would be disadvantaged in pursuing it from the UK.
"We understand the EU is not perfect, but we hope the UK can continue from inside to change it for the better.
"Strong national policy and membership of Europe can go together.
"From our viewpoint, attracting foreign investment and high-value job creation depends on staying in and continuing to create a competitive internal market, and in this we hope the UK will be the leading force it has always been."